Single-subject activation studies involving passive stimuli that were varied in measurable ways (parametrically) were designed to examine brain networks and synaptic integrity in healthy subjects and subjects with Alzheimer's disease (AD) and Down syndrome (DS), and to see how pharmacological agents can modify these parameters. Regional cerebral blood flow (rCBF) was measured during stimulation, using positron emission tomography (PET) with 15O-water or functional magnetic resonance imaging (fMRI). Stimulation involving alternating flashes to both eyes, at different frequencies, demonstrated increasing rCBF responses with frequencies to 7 Hz in the primary visual cortex of normal subjects, but only to 4 Hz in AD patients; and responsiveness at 1 Hz in the middle temporal cortex of normal but not of AD subjects, indicating selective pathology in the magnocellular compared with the parvocellular visual pathway in AD. Data were analyzed by a new regions of interest method involving coregistration of PET and MR, taking into account atrophy. In another study, textured visual patterns were presented passively to young healthy subjects in relation to pattern organization, while using 15O-water PET. Two visual textures with the same black-white load produced different rCBF response patterns in the visual cortex. The observations were confirmed by fMRI. Thus, there are distinct form networks involved in texture perception, which can now be examined in noncompliant subjects.